Biology & Medicine News and Discussions

weatheriscool
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Spleen function discovery could lead to better treatments for infectious diseases

by Robyn Riley, University of Melbourne
https://medicalxpress.com/news/2022-01- ... tious.html
Researchers at the Peter Doherty Institute for Infection and Immunity (Doherty Institute) have discovered a new gene that plays an important role in the way the spleen functions, potentially leading to new treatments for infectious diseases.

The study, published in Science Immunology, also uncovered multiple new spleen cells and revealed the distinct way they respond in order to fight off different infections.

The spleen plays a key role in the immune responses that protect the body against various diseases and infections such as virus infections, malaria and sepsis, and also plays a key role in the immune response to vaccines. However, it has not been known how the spleen functions to support this response.

University of Melbourne Professor Scott Mueller, a Laboratory Head at the Doherty Institute and lead author on the paper, explained that while it is known the spleen is made up of various networks of cells called fibroblasts, a clear picture of how these cells are constructed and function, was lacking.

"Using novel biological tools and next generation sequencing, we were able to examine precisely how specialized types of fibroblast cells dictate how the spleen works to protect against infections," Professor Mueller explained.

"We performed next-generation sequencing to understand what genes are expressed by fibroblasts in the spleen. We used advanced fluorescent microscopy to visualize the 3D networks of cells in the spleen.
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First images of enzyme provide insights into cause of hereditary neurological disease
https://phys.org/news/2022-01-images-en ... gical.html
by Walter and Eliza Hall Institute of Medical Research
WEHI researchers have produced the first molecular images of an enzyme that controls proteins to signal and communicate with each other in human cells. The discovery could help to solve the mystery cause of a rare group of hereditary neurodegenerative diseases linked to deregulation of this enzyme.

In the study, published in Molecular Cell, Dr. Thomas Cotton, Dr. Bernhard Lechtenberg and colleagues at WEHI solved the first three-dimensional (3D) structure of an enzyme called RNF216. The team captured molecular 'snapshots' of RNF216 as it assembled chains of the small protein ubiquitin, which tags the target proteins to modify their behavior in the cell. They also showed how RNF216 dictates the type of ubiquitin chain that is formed—the first time that this has been explained.

Mutations in RNF216 have been linked to Gordon-Holmes Syndrome, a very rare neurodegenerative disorder that results in reproductive problems, movement disorders, and progressive cognitive decline and dementia.
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In 1st, US surgeons transplant pig heart into human patient
Source: AP

By CARLA K. JOHNSON

In a medical first, doctors transplanted a pig heart into a patient in a last-ditch effort to save his life and a Maryland hospital said Monday that he’s doing well three days after the highly experimental surgery.

While it’s too soon to know if the operation really will work, it marks a step in the decades-long quest to one day use animal organs for life-saving transplants. Doctors at the University of Maryland Medical Center say the transplant showed that a heart from a genetically modified animal can function in the human body without immediate rejection.

The patient, David Bennett, a 57-year-old Maryland handyman, knew there was no guarantee the experiment would work but he was dying, ineligible for a human heart transplant and had no other option, his son told The Associated Press.

“It was either die or do this transplant. I want to live. I know it’s a shot in the dark, but it’s my last choice,” Bennett said a day before the surgery, according to a statement provided by the University of Maryland School of Medicine.
https://storage.googleapis.com/afs-prod ... 728cfb2d/1

In this photo provided by the University of Maryland School of Medicine, members of the surgical team show the pig heart for transplant into patient David Bennett in Baltimore on Friday, Jan. 7, 2022. On Monday, Jan. 10, 2022 the hospital said that he's doing well three days after the highly experimental surgery. (Mark Teske/University of Maryland School of Medicine via AP)
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Read more: https://apnews.com/article/pig-heart-tr ... ecb6449aef
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Researchers develop new method to increase effectiveness of nanomedicines
https://phys.org/news/2022-01-method-ef ... cines.html
by Perelman School of Medicine at the University of Pennsylvania
Researchers at Penn Medicine have discovered a new, more effective method of preventing the body's own proteins from treating nanomedicines like foreign invaders, by covering the nanoparticles with a coating to suppress the immune response that dampens the therapy's effectiveness.

When injected into the bloodstream, unmodified nanoparticles are swarmed by elements of the immune system called complement proteins, triggering an inflammatory response and preventing the nanoparticles from reaching their therapeutic targets in the body. Researchers have devised some methods to reduce this problem, but the Penn Medicine team, whose findings are published in Advanced Materials, has invented what may be the best method yet: coating nanoparticles with natural suppressors of complement activation.

Nanoparticles are tiny capsules, typically engineered from proteins or fat-related molecules, that serve as delivery vehicles for certain types of treatment or vaccine—usually those containing RNA or DNA. The best-known examples of nanoparticle-delivered medicines are mRNA vaccines against COVID-19.

"It turned out to be one of those technologies that just works right away and better than anticipated," said study co-senior author Jacob Brenner, MD, Ph.D., an associate professor of Pulmonary Medicine in the Division of Pulmonary, Allergy, and Critical Care.
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Genetically engineered E. coli could improve drug development
https://phys.org/news/2022-01-genetical ... -drug.html
by Michelle Revels, Texas A&M University College of Engineering
Whether you are taking a muscle relaxant or a heart medication, you are possibly using a medication that contains a synthetically produced benzoxazole. Although natural benzoxazoles show more significant promise in pharmaceuticals, their time to develop organically and inherent undesired properties impede their usage.

Dr. Xuejun Zhu, assistant professor in the Artie McFerrin Department of Chemical Engineering at Texas A&M University, alongside graduate student Huanrong Ouyang, and two undergraduate students, Joshua Hong and Jeshua Malroy are synthesizing natural benzoxazoles using E. coli in hopes of developing a more efficient, eco-friendly and cost-effective method of producing them for future drug development.

Their research was published in the American Chemical Society's journal ACS Synthetic Biology 2021.

Benzoxazole is a heterocyclic compound composed of carbon, hydrogen, oxygen and nitrogen. It can be produced synthetically but is also found in bioactive natural products like nataxazole, caboxamycin and calcimycin. Synthetically created benzoxazoles are found in synthetic pharmaceuticals ranging from chlorzoxazone (a muscle relaxant) to tafamidis (for treating heart disease).
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caltrek
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Personalized Medicine - Functioning, Induced Liver Cells from Skin Tissue
January 16, 2022

https://www.eurekalert.org/news-releases/936709

Introduction:
(EurekAlert) The urea cycle is responsible for removing nitrogenous waste produced from the breakdown of protein in the organism. If the OTC enzyme is missing in this cycle, ammonia accumulation rises to toxic levels. An OTC deficiency is the most common disorder in the urea cycle. It could not be cured with drugs until now.

The OTC gene is located on the sex chromosome (X chromosome). This means that the manifestation of the disorder is usually weaker in female newborns. However, in male newborns, who have one X and one Y chromosome, a deficiency in the OTC gene has a dramatic effect: In newborn boys, ammonia toxicity due to OTC deficiency is often fatal. The research team looked for ways to test drugs in the lab against the OTC deficiency.

Created an initial model

First the research team generated liver cells from patients’ skin tissue in an elaborate process. It worked like this: Initially, a tissue sample of the skin was taken from OTC-deficient patients as well as from a control group (healthy individuals). In a complex process, the samples were differentiated so that they functioned like stem cells. This engineering process was developed by Shin’Ya Yamanaka, for which he was awarded the Nobel Prize in Medicine in 2012. “By using induced stem cell technology, we succeeded in generating liver cells that function largely like liver cells from patients,” explains Dr. med. Alexander Lämmle, Senior Physician at the Department of Pediatrics and the University Institute of Clinical Chemistry at Inselspital. “However, we observed that the induced liver cells excrete significantly less urea than real, healthy liver cells, and this is independent of whether they originate from healthy controls or urea cycle patients.” The researchers were able to determine the reason for this behavior. The technologically engineered stem cells were characterized by a complete lack of aquaporin 9, a transport protein in the cell membrane. The reason for this deficiency is the still immature, fetal character of the artificial liver cells.
Aquaporin 9: the key to a functioning artificial liver cell,

Aquaporins organize the transport of water and certain substances through the cell membrane. Aquaporin 9 is responsible for the transport of urea...
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Scientists identify therapeutic target for Epstein-Barr virus
https://phys.org/news/2022-01-scientist ... virus.html
by The Wistar Institute
A new study by researchers at The Wistar Institute, an international biomedical research leader in cancer, immunology, infectious disease, and vaccine development, has identified a new potential pathway for developing therapeutics that target Epstein-Barr virus (EBV). They discovered that the way the EBV genome folds, and thereby expresses itself and causes disease, is more complex than researchers originally thought, and they identified molecules that could be targeted to disrupt this folding.

"We identified two cellular proteins that are important to folding the EBV genome." said Italo Tempera, Ph.D., associate professor in the Gene Expression & Regulation Program at The Wistar Institute and corresponding author on the paper. "There are existing drugs that target one of these proteins. And our data suggests that if we use that drug on EBV infected cells, we have a way in which we can actually interfere with the folding. That means we can interfere in the way in which the EBV viral genome is functioning."
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Special Phage Therapy Clears a Patient's Resistant Infection After 798 Days
by Conor Feehly
January 21, 2022

https://www.sciencealert.com/case-study ... -superbugs

Introduction:
(Science Alert) After 700 days of antibiotic treatment, the infection of a 30-year-old bombing attack victim still raged.

Tragically, the patient had suffered life-threatening injuries during the attacks at Brussels airport on 22 March 2016. Over the next three years, she faced numerous medical complications, as her fracture-related wound became infected with pan-drug-resistant bacteria, or what we know colloquially as superbugs.

Confronted with little progress, clinicians decided to turn to a combination of antibiotics and specialized bacteriophage therapy, a new treatment that harnesses specialized viruses that infect and kill bacteria. Her unique and successful case has now been described in Nature Communications.

Superbug infections are becoming an increasingly serious health issue, with phage therapy being amongst the most promising new tools in our arsenal.

Normally, phages infect a subset of strains of bacteria that belong to a single bacterial species, however, clinicians have been working on personalized forms of phage therapy, where phages from a prepared bank are selected by analyzing the bacterial strains isolated from the patient's bacterial infection.
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Scientists discover new avian immunological pathway
https://medicalxpress.com/news/2022-01- ... thway.html
by University of California - Riverside

A research team led by a biomedical scientist at the University of California, Riverside, has discovered a new immune pathway in chickens that viruses—such as those that tend to infect birds, humans, and animals and spread diseases like influenza or Crimean-Congo hemorrhagic fever—may be targeting.

The discovery, which has implications also for diseases affecting other birds, sheds greater light on birds' immune responses to zoonotic viruses—specifically, how those may differ from responses seen in humans.

"Understanding these differences is critical to better understanding birds as potential reservoirs of human pathogens," said Scott Pegan, a professor of biomedical sciences in the UC Riverside School of Medicine, who led the study published in Frontiers in Immunology. "Additionally, it allows researchers to better understand the immune pathways that might lead to effective vaccines for agriculture use in poultry."
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Robot performs first laparoscopic surgery without human help
https://techxplore.com/news/2022-01-rob ... human.html
by Johns Hopkins University
A robot has performed laparoscopic surgery on the soft tissue of a pig without the guiding hand of a human—a significant step in robotics toward fully automated surgery on humans. Designed by a team of Johns Hopkins University researchers, the Smart Tissue Autonomous Robot (STAR) is described today in Science Robotics.

"Our findings show that we can automate one of the most intricate and delicate tasks in surgery: the reconnection of two ends of an intestine. The STAR performed the procedure in four animals and it produced significantly better results than humans performing the same procedure," said senior author Axel Krieger, an assistant professor of mechanical engineering at Johns Hopkins' Whiting School of Engineering.

The robot excelled at intestinal anastomosis, a procedure that requires a high level of repetitive motion and precision. Connecting two ends of an intestine is arguably the most challenging step in gastrointestinal surgery, requiring a surgeon to suture with high accuracy and consistency. Even the slightest hand tremor or misplaced stitch can result in a leak that could have catastrophic complications for the patient.
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